Fig. 7.

YTHDC2 suppression was sensitive to system X_C^--targeting therapy and associated with LUAD progression. (A) Percentages of the indicated subtypes in cohort#1 LUAD with the YTHDC2^low expression pattern. (B) YTHDC2 protein levels in paired acinar LUAD tissues (cohort #2), as measured by ELISA. (C) Percentages of LUAD with the YTHDC2^low expression pattern in acinar LUAD (cohort #2). (D) Overall survival in acinar LUAD (cohort #2) with or without the YTHDC2^low expression pattern (log-rank test, p = 0.0009). (E, F) SLC7A11 mRNA and protein levels were measured in paired acinar LUAD tissues (cohort #2) using RT-qPCR and ELISA assay. (G–J) Tumor volume was calculated in PDX mice models administrated with DMSO, PKE (20 mg/kg/day) or sorafenib (80 mg/kg/day) at the indicated time points. (K, L) MDA and 4-HNE levels were detected using lipid peroxidation assay kit in PDX tumors. (M, N) MDA, YTHDC2 protein levels, SLC7A11 protein and mRNA levels were measured by lipid peroxidation assay, ELISA, and RT-qPCR in cohorts #3 and #4. Statistical analysis was performed using Student's t tests (B, E, F, M), two-way ANOVA (G–J) and one-way ANOVA (K, L, N). Data are means ± SEMs, **p < 0.01.